Noncoding RNAs As Promising Diagnostic Biomarkers and Therapeutic Targets in Intestinal Fibrosis of Crohn's Disease: The Path From Bench to Bedside

Overview

Journal Inflamm Bowel Dis

Publisher Oxford University Press

Specialty Gastroenterology

Date 2020 Dec 16

PMID 33324986

Citations 6

Authors

Long-Yuan Zhou

Si-Nan Lin

Florian Rieder

Min-Hu Chen

Sheng-Hong Zhang

Ren Mao

Affiliations

Soon will be listed here.

Abstract

Fibrosis is a major pathway to organ injury and failure, accounting for more than one-third of deaths worldwide. Intestinal fibrosis causes irreversible and serious clinical complications, such as strictures and obstruction, secondary to a complex pathogenesis. Under the stimulation of profibrotic soluble factors, excessive activation of mesenchymal cells causes extracellular matrix deposition via canonical transforming growth factor-β/Smads signaling or other pathways (eg, epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition) in intestinal fibrogenesis. In recent studies, the importance of noncoding RNAs (ncRNAs) stands out in fibrotic diseases in that ncRNAs exhibit a remarkable variety of biological functions in modulating the aforementioned fibrogenic responses. In this review, we summarize the role of ncRNAs, including the emerging long ncRNAs and circular RNAs, in intestinal fibrogenesis. Notably, the translational potential of ncRNAs as diagnostic biomarkers and therapeutic targets in the management of intestinal fibrosis is discussed based on clinical trials from fibrotic diseases in other organs. The main points of this review include the following: • Characteristics of ncRNAs and mechanisms of intestinal fibrogenesis • Wide participation of ncRNAs (especially the emerging long ncRNAs and circular RNAs) in intestinal fibrosis, including transforming growth factor-β signaling, epithelial-to-mesenchymal transition/endothelial-to-mesenchymal transition, and extracellular matrix remodeling • Translational potential of ncRNAs in the diagnosis and treatment of intestinal fibrosis based on clinical trials from fibrotic diseases in other organs.

Citing Articles

The Diagnosis of Intestinal Fibrosis in Crohn's Disease-Present and Future.

Jarmakiewicz-Czaja S, Gruszecka J, Filip R Int J Mol Sci. 2024; 25(13).

PMID: 39000043 PMC: 11241173. DOI: 10.3390/ijms25136935.

Prospective therapeutics for intestinal and hepatic fibrosis.

Li X, Yu M, Zhao Q, Yu Y Bioeng Transl Med. 2023; 8(6):e10579.

PMID: 38023697 PMC: 10658571. DOI: 10.1002/btm2.10579.

Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition.

Macias-Ceja D, Mendoza-Ballesteros M, Ortega-Albiach M, Barrachina M, Ortiz-Masia D Front Cell Dev Biol. 2023; 11:1258843.

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Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease.

Velissari R, Ilieva M, Dao J, Miller H, Madsen J, Gorodkin J Brief Funct Genomics. 2023; 23(4):395-405.

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Fibro-Stenosing Crohn's Disease: What Is New and What Is Next?.

Solitano V, Dal Buono A, Gabbiadini R, Wozny M, Repici A, Spinelli A J Clin Med. 2023; 12(9).

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References

Zhi S, Chen S, Li Y, Li J, Zheng Y, Yu F . Rosiglitazone Inhibits Activation of Hepatic Stellate Cells via Up-Regulating Micro-RNA-124-3p to Alleviate Hepatic Fibrosis. Dig Dis Sci. 2019; 64(6):1560-1570. DOI: 10.1007/s10620-019-5462-8. View

Zhou Y, Deng L, Zhao D, Chen L, Yao Z, Guo X . MicroRNA-503 promotes angiotensin II-induced cardiac fibrosis by targeting Apelin-13. J Cell Mol Med. 2016; 20(3):495-505. PMC: 4759464. DOI: 10.1111/jcmm.12754. View

Yu F, Lu Z, Cai J, Huang K, Chen B, Li G . MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis. Cell Cycle. 2015; 14(24):3885-96. PMC: 4825734. DOI: 10.1080/15384101.2015.1120917. View

Zile M, Mehurg S, Arroyo J, Stroud R, DeSantis S, Spinale F . Relationship between the temporal profile of plasma microRNA and left ventricular remodeling in patients after myocardial infarction. Circ Cardiovasc Genet. 2011; 4(6):614-9. PMC: 3535326. DOI: 10.1161/CIRCGENETICS.111.959841. View

Rieder F, Fiocchi C . Intestinal fibrosis in IBD--a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol. 2009; 6(4):228-35. DOI: 10.1038/nrgastro.2009.31. View

Liu X, Pan Q, Zhang R, Shen F, Yan S, Sun C . Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population. World J Gastroenterol. 2016; 22(44):9844-9852. PMC: 5124990. DOI: 10.3748/wjg.v22.i44.9844. View

Mehta S, Lewis A, Nijhuis A, Jeffery R, Biancheri P, Di Sabatino A . Epithelial down-regulation of the miR-200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition. J Cell Mol Med. 2018; 22(11):5617-5628. PMC: 6201355. DOI: 10.1111/jcmm.13836. View

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

Thomas A, Biswas S, Feng B, Chen S, Gonder J, Chakrabarti S . lncRNA H19 prevents endothelial-mesenchymal transition in diabetic retinopathy. Diabetologia. 2019; 62(3):517-530. DOI: 10.1007/s00125-018-4797-6. View

10.

Trebicka J, Anadol E, Elfimova N, Strack I, Roggendorf M, Viazov S . Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis. J Hepatol. 2012; 58(2):234-9. DOI: 10.1016/j.jhep.2012.10.015. View

11.

Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M . MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456(7224):980-4. DOI: 10.1038/nature07511. View

12.

Iacob D, Rosca A, Ruta S . Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis. World J Gastroenterol. 2020; 26(11):1113-1127. PMC: 7093315. DOI: 10.3748/wjg.v26.i11.1113. View

13.

Nonaka C, Macedo C, Cavalcante B, Alcantara A, Silva D, da Rocha Bezerra M . Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy. Int J Mol Sci. 2019; 20(16). PMC: 6721092. DOI: 10.3390/ijms20164064. View

14.

Roderburg C, Urban G, Bettermann K, Vucur M, Zimmermann H, Schmidt S . Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology. 2010; 53(1):209-18. DOI: 10.1002/hep.23922. View

15.

Haberman Y, BenShoshan M, Segni A, Dexheimer P, Braun T, Weiss B . Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease. Inflamm Bowel Dis. 2018; 24(2):346-360. PMC: 6231367. DOI: 10.1093/ibd/izx013. View

16.

Louafi F, Martinez-Nunez R, Sanchez-Elsner T . MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}. J Biol Chem. 2010; 285(53):41328-36. PMC: 3009858. DOI: 10.1074/jbc.M110.146852. View

17.

Yue B, Liu C, Sun H, Liu M, Song C, Cui R . A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/β-Catenin Signaling Promotes Metastasis of Colon Cancer. Mol Ther. 2018; 26(5):1287-1298. PMC: 5993983. DOI: 10.1016/j.ymthe.2018.02.024. View

18.

Yu F, Chen B, Dong P, Zheng J . HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis. Mol Ther. 2017; 25(1):205-217. PMC: 5363197. DOI: 10.1016/j.ymthe.2016.10.015. View

19.

Jin J, Zhai H, Jia Z, Luo X . Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling. Am J Physiol Cell Physiol. 2019; 317(5):C1001-C1010. DOI: 10.1152/ajpcell.00319.2018. View

20.

Chung A, Huang X, Meng X, Lan H . miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. J Am Soc Nephrol. 2010; 21(8):1317-25. PMC: 2938591. DOI: 10.1681/ASN.2010020134. View